MELANOCYTE TUMOR PROGRESSION IS ASSOCIATED WITH CHANGES IN ANGIOGENESIS AND EXPRESSION OF THE 67-KILODALTON LAMININ RECEPTOR

Background. A number of experimental studies have substantiated change s in angiogenesis and in laminin/laminin-receptor interactions during tumorigenesis and tumor progression. However, these observations have never been verified objectively in tissues from a well-defined model o f tumor progression. Methods. Tissues from 97 proliferative lesions of the melanocyte lineage defining distinct steps in tumor progression w ere investigated immunohistochemically for changes in angiogenesis and expression of the laminin receptor (67-kilodalton molecule). Results. Although the microvessel number was low in common nevi, it increased significantly in nevi with architectural disorder with varying degrees of melanocytic atypia (termed ''nevi with ADMA''), and these changes persisted during transformation. Progression to primary melanomas was accompanied by a high microvessel number and progression to metastases by another significant increase. The number and diameter of microvess els were significantly higher at the lesion base than at the adjacent dermis of primary melanomas and higher in the lesion than in the adjac ent tissue of metastatic foci. Expression of the laminin receptor, eva luated as percentages of positive lesions and positive cells per lesio n, underwent upregulation in the course of progression. Changes in exp ression were associated mostly with nevi with ADMA, transformation, an d deepening of the tumors into the dermis. Conclusions. These in situ data suggest that more frequent interactions between melanocytic cells and their microvasculature via adhesion protein laminin occur during tumor progression.